Lipid membranes have heretofore been used as detection membranes or the like in sensors or measuring devices. For example, they have been used for the detection or assay of various substances such as metal ions, cyanide ions, alcohols and enzymes.
Lipid membranes have also been used for evaluating the permeability of biomembranes which mediate various reactions in the body, e.g., substance and/or energy transfer, metabolism, signal transduction, etc.
For example, the permeability of drugs across lipid membranes is closely related to gastrointestinal absorption and in vivo trans-tissue delivery of oral formulations, so it is a critical property in developing pharmaceuticals. In addition to drugs, it is also critical to evaluate the membrane permeability of substances which adversely affect living organisms (e.g., toxic substances, carcinogenic substances, etc.).
To determine the membrane permeability of substances in the body by an in vitro technique, there is a need to use a membrane whose permeability to substances is strongly correlated with the in vivo permeability of biomembranes to substances. In addition to this, throughput speed and cost are critical requirements for industrial application of such membranes. For example, when such a membrane is used to evaluate the membrane permeability of drugs in pharmaceutical development, the membrane is required to provide high throughput speed because a numerous number of compounds are required to be screened.
For in vitro determination of the membrane permeability of substances, several techniques are conventionally used, such as a technique using isolated organs, a technique using intestinal epithelium-derived cells, etc. However, because of their low throughput speed, these techniques are unable to provide rapid screening of a large number of substances.
Other techniques are also known for this purpose, e.g., an artificial membrane permeation assay using an artificial lipid membrane formed on a 96-well plate (see Manfred KANSY, Frank SENNER, Klaus GUBERNATOR; Journal of Medicinal Chemistry 1998, 41, 1007-1010). A lipid membrane prepared from a lipid(s) and an organic solvent(s) is used as an artificial lipid membrane in this technique. Major features of this technique include, for example, the ability to perform a parallel assay of many substances at the same time and low running cost due to the need to use only a small amount of substances for assay. However, the membrane used in the disclosed technique is disadvantageous in that it not only has a weak correlation with the in vivo permeability of biomembranes to substances, but it also involves difficulty in evaluating low-permeability substances and requires a long time for evaluation because the membrane is less permeable to substances.
Membranes used for measuring the membrane permeability of substances are known from, for example, Ken-ichi INUI, Katsue TABARA, Ryohei HIRI, Akemi KANEDA, Shozo MURANISHI, Hitoshi SEZAKI; Journal of Pharmacy and Pharmacology, 1977, 29, 22-26, which discloses a membrane that is prepared from living organism (rat) derived-membrane components dissolved in n-decane. This membrane is characterized by having a strong correlation with the permeability of biomembranes to substances, but it is still disadvantageous in that it involves difficulty in evaluating low-permeability substances and requires a long time for evaluation because the membrane is less permeable to substances.
Also, a membrane prepared from dodecane, phosphatidylcholine and 1,9-decadiene is known from Manfred KANSY, Frank SENNER, Klaus GUBERNATOR; Journal of Medicinal Chemistry 1998, 41, 1007-1010. However, such a membrane is similarly disadvantageous in that it requires a long time for measurement and involves difficulty in distinguishing between low-permeability substances because the membrane is less permeable to substances and a further disadvantage is in that it has a weak correlation with the permeability of biomembranes to substances.